SOUTH SAN FRANCISCO, Calif.--(EON: Enhanced Online News)--Exelixis, Inc. (NASDAQ:EXEL) today reported data from the phase 3
pivotal trial of cabozantinib in patients with progressive,
unresectable, locally advanced or metastatic medullary thyroid cancer
(MTC). The trial, known as EXAM, met its primary endpoint of improving
progression-free survival (PFS), with patients in the cabozantinib arm
achieving a median PFS of 11.2 months compared with 4.0 months for
patients in the placebo arm. Overall response rate (ORR), a secondary
endpoint, was 28% in the cabozantinib arm and 0% in the placebo arm.
Estimated PFS at one year was 47.3% with cabozantinib vs. only 7.2% with
placebo. Data for overall survival (OS), another secondary endpoint, are
not yet mature. Patients on the cabozantinib arm of the trial received a
dose of 140 mg (free base equivalent). Adverse events were generally
manageable allowing for treatment with cabozantinib for prolonged
periods of time. Exelixis recently submitted a New Drug Application
(NDA) for cabozantinib in MTC to the U.S. Food and Drug Administration
(FDA).

“As the first phase 3 trial to enroll patients with independently
confirmed radiographic progressing medullary thyroid cancer, EXAM
represents an important milestone for this orphan disease in which there
have been very few rigorous prospective clinical trials”

Dr. Patrick Schöffski, professor at the Department of General Medical
Oncology at the University Hospitals of Leuven, Catholic University
Leuven, Belgium, presented the data (Abstract #5508) today in an oral
session at the 2012 Annual Meeting of the American Society of Clinical
Oncology (ASCO) in Chicago, Illinois. The slides from the presentation
are available at http://www.exelixis.com/resources/events/asco-2012.

“As the first phase 3 trial to enroll patients with independently
confirmed radiographic progressing medullary thyroid cancer, EXAM
represents an important milestone for this orphan disease in which there
have been very few rigorous prospective clinical trials,” said Dr.
Schöffski. “The data presented today are highly compelling and
demonstrate that cabozantinib can provide a significant benefit to
patients with advanced MTC. Taken as a whole, the results clearly show
that cabozantinib is an important advance in the treatment of MTC and
has the potential to improve the care and outcomes for MTC patients.”

Efficacy Results

All 330 patients were included in the efficacy analysis. Cabozantinib
met the primary endpoint of the trial, with a median PFS of 11.2 months
vs. 4.0 months for placebo [HR 0.28, p<0.0001] based on the independent
radiology committee (IRC) evaluation. The Kaplan Meier estimate for the
proportion of patients alive and progression-free at 1 year was 47.3% in
the cabozantinib arm and 7.2% in the placebo arm. Other sensitivity
analyses (investigator assessment, uniform date, and per protocol
assessment) were consistent with the primary analysis.Cabozantinib’s
benefit on PFS was seen across a number of pre-specified subgroups
including RET mutational status or prior tyrosine kinase inhibitor (TKI)
therapy.With respect to secondary endpoints, the ORR, per RECIST
evaluated by the IRC, was 28% in the cabozantinib arm and 0% in the
placebo group. Median duration of response was 14.6 months.At
the time of the June 2011 data cut-off, 44% of the events required for
the OS analysis had occurred, making data on overall survival immature.
At the time of the interim analysis, no difference in OS was observed
between treatment arms. A final OS analysis will be conducted after 217
events have occurred.

“As seen in the initial topline results, and again today at the ASCO
Annual Meeting, cabozantinib delivered a nearly three-fold increase in
median PFS in the EXAM trial,” said Michael M. Morrissey, Ph.D.,
president and chief executive officer of Exelixis. “The trial was
conducted under a Special Protocol Assessment with the FDA, with
progression-free survival as the primary endpoint, and we completed the
submission of our NDA for MTC at the end of May. Beyond MTC, we are also
excited about the encouraging interim cabozantinib data that have been
generated in a variety of other tumor indications, including
hepatocellular carcinoma, renal cell carcinoma and castration-resistant
prostate cancer, which are the subjects of oral presentations at this
year’s ASCO Annual Meeting. In particular, the prostate cancer data
formed the basis for advancing cabozantinib into two recently initiated
phase 3 pivotal trials, COMET-1 and COMET-2.”

Patient Demographics

The trial enrolled 330 patients with locally advanced or metastatic MTC
that had progressed per RECIST within 14 months of screening. Patients
were randomized 2:1 to cabozantinib (N=219) or placebo (N=111). Median
age in both arms was 54 years, and almost all patients had ECOG
performance status of 0-1 (95% and 90% in the cabozantinib and placebo
arms, respectively). Prior TKI exposure (20%, 22%), measurable disease
(95%, 94%), and bone metastases at baseline (each 51%) were also
balanced between the cabozantinib and placebo arms, respectively. RET
mutations were seen at a similar rate between arms (46%, 52%).

As of the June 15, 2011 data cut off date, 45% of cabozantinib-treated
and 13% of placebo-treated patients were still receiving study
treatment. 60% of placebo-treated patients discontinued treatment for
progressive disease, compared with 26% of cabozantinib-treated patients.
16% of patients on the cabozantinib arm had discontinued treatment for
an AE compared to 8% of patients on the placebo arm. 5% of patients on
both arms discontinued for death. 12% of patients on the placebo arm
discontinued study treatment because of subject request compared to 4%
on the cabozantinib-treated arm.

Safety Results

The safety analysis included the 323 patients in both arms of the trial
who had received at least one dose of study treatment (214 in the
cabozantinib arm and 109 in the placebo arm). Consistent with the much
longer PFS, the median duration of exposure was twice as long in the
cabozantinib arm (6.7 months) versus the placebo arm (3.4 months).

Overall AE results for the trial are consistent with a long duration of
exposure to an active agent in a patient population with advanced
disease. The most frequent adverse events (AEs) of grade ≥ 3 with
greater than 2% incidence in the cabozantinib arm were: diarrhea (16%),
palmar-plantar erythrodysesthesia (13%), fatigue (9%), hypertension
(8%), decreased weight (5%), decreased appetite (5%), and stomatitis
(2%). The most frequent adverse events (AEs) of grade ≥ 3 with greater
than 2% incidence in the placebo arm were: diarrhea (2%) and fatigue
(2%). Diarrhea and decreased weight are commonly associated with
advanced and progressive MTC.

Cabozantinib is a potent inhibitor of vascular endothelial growth factor
receptor 2 (VEGFR2), and investigators reported infrequent adverse
events that have previously been associated with VEGF-pathway
inhibition. Grade ≥ 3 adverse events in the cabozantinib arm that are
generally associated with VEGF-pathway inhibition were: hypertension
(8%), venous thrombosis (4%), hemorrhage (3%), GI perforation (3%), and
non-GI fistula (2%). In some cases, these events may also be the result
of an anti-tumor effect. For example, two patients who experienced
non-GI fistulas had involvement of the lungs or bronchus and had partial
responses.

Deaths were generally balanced between treatment arms, and most were due
to progressive disease. Deaths for reasons other than progressive
disease and within 30 days of treatment cessation occurred in 5.6% of
patients on the cabozantinib arm and in 2.8% of patients on the placebo
arm. The difference is largely accounted for by 1.9% of the total number
of deaths in the cabozantinib arm that were due to events commonly
associated with VEGF-pathway inhibition.

Biochemical Response Results

Biochemical responses assessed as additional secondary endpoints were
consistent with the observed anti-tumor activity of cabozantinib.
Calcitonin levels dropped by 45% in the cabozantinib arm, but rose by
57% in the placebo arm during the first three months on study.Similar
effects were seen with CEA.

EXAM Trial Design

EXAM is an international, randomized, placebo-controlled, double-blinded
study of cabozantinib in patients with progressive, unresectable,
locally advanced, or metastatic MTC. The study enrolled 330 patients who
were randomized in a 2:1 ratio to receive cabozantinib (N=219) or
placebo (N=111) administered at a daily dose of 140 mg (free base
equivalent). The study did not allow for crossover from the placebo arm
to cabozantinib. The first patient was randomized in October 2008 and
the last patient was randomized in February 2011. The trial provided 90%
power to detect a 75% increase in PFS, the primary endpoint of the
study. Additionally, the study is designed to assess OS once the
appropriate number of events have occurred, and has 80% to detect a 50%
improvement in survival compared with placebo. Exelixis conducted this
trial under a SPA from the FDA, which allows for full approval on the
basis of PFS if the data are supportive.

About Cabozantinib

Cabozantinib is a potent targeted therapy that inhibits MET, VEGFR2, and
RET, all of which play an important role in the biology of medullary
thyroid cancer. Cabozantinib is an investigational agent that provides
coordinated inhibition of metastasis and angiogenesis to kill tumor
cells while blocking their escape pathways. The therapeutic role of
cabozantinib is currently being investigated across several tumor types.
MET is upregulated in many tumor types, thus facilitating tumor cell
escape by promoting the formation of more aggressive phenotypes,
resulting in metastasis. MET-driven metastasis may be further stimulated
by hypoxic conditions in the tumor environment, which are often
exacerbated by selective VEGF-pathway inhibitors. In preclinical
studies, cabozantinib has shown powerful tumoricidal, antimetastatic and
antiangiogenic effects, including:

Extensive apoptosis of malignant cells

Decreased tumor invasiveness and metastasis

Decreased tumor and endothelial cell proliferation

Blockade of metastatic bone lesion progression

Disruption of tumor vasculature

About Exelixis

Exelixis, Inc. is a biotechnology company committed to developing small
molecule therapies for the treatment of cancer. Exelixis is focusing its
proprietary resources and development efforts exclusively on
cabozantinib (XL184), its most advanced product candidate, in order to
maximize the therapeutic and commercial potential of this compound.
Exelixis believes cabozantinib has the potential to be a high-quality,
broadly-active, differentiated pharmaceutical product that can make a
meaningful difference in the lives of patients. Exelixis has also
established a portfolio of other novel compounds that it believes have
the potential to address serious unmet medical needs, many of which are
being advanced by partners as part of collaborations. For more
information, please visit the company's web site at http://www.exelixis.com.

Forward-Looking Statements

This press release contains forward-looking statements, including,
without limitation, statements related to: the continued development and
clinical, therapeutic and commercial potential of, and opportunities
for, cabozantinib; the belief that EXAM represents an important
milestone and advance for the treatment of MTC; the belief that the
referenced data are highly compelling and demonstrate that cabozantinib
can provide a significant clinical benefit to patients with advanced
MTC; the belief that MTC has the potential to improve the care and
outcomes for MTC patients; potential approval by the FDA of the
referenced NDA; and encouraging cabozantinib data generated in other
tumor indications. Words such as “milestone,” “compelling,”
“demonstrate,” “can,” “advance,” “potential,” “encouraging,” “believes,”
and similar expressions are intended to identify forward-looking
statements. These forward-looking statements are based upon Exelixis'
current plans, assumptions, beliefs and expectations. Forward-looking
statements involve risks and uncertainties. Exelixis' actual results and
the timing of events could differ materially from those anticipated in
such forward-looking statements as a result of these risks and
uncertainties, which include, without limitation: risks related to the
potential failure of cabozantinib to demonstrate safety and efficacy in
clinical testing; Exelixis' ability to conduct clinical trials of
cabozantinib sufficient to achieve a positive completion; the
availability of data at the referenced times; the sufficiency of
Exelixis' capital and other resources; the uncertain timing and level of
expenses associated with the development of cabozantinib; the
uncertainty of the FDA approval process; timely receipt of potential
reimbursements, milestones, royalties and profits under Exelixis’
collaborative agreements; Exelixis’ ability to enter into new
collaborations; market competition; and changes in economic and business
conditions. These and other risk factors are discussed under "Risk
Factors" and elsewhere in Exelixis' quarterly report on Form 10-Q for
the quarter ended March 30, 2012 and Exelixis' other filings with the
Securities and Exchange Commission. Exelixis expressly disclaims any
duty, obligation or undertaking to release publicly any updates or
revisions to any forward-looking statements contained herein to reflect
any change in Exelixis' expectations with regard thereto or any change
in events, conditions or circumstances on which any such statements are
based.

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